The objective of this program is to gain further insight into changes in selected biochemical regulatory systems during aging. The biochemical fate of insulin molecules is being studied in aging Sprague-Dawley rats. This effort includes isolation and translation of (pre) proinsulin mRNA, synthesis and metabolism of proinsulin to insulin, and secretion and efficacy of various hormone forms and metabolites. The integrity of the glucocorticoid receptor system is being examined in liver of Sprague-Dawley rats throughout their lifespan. This study focusses on activation of the hormone-receptor complex for nuclear transfer, as well as metabolic fate of the receptor in the nucleus. The final project concerns an inverse correlation between susceptibility of cultured skin fibroblasts to chemically induced mutagenesis and the lifespan of mammalian species from which the cells are derived. Current efforts focus on the metabolism of various polycyclic hydrocarbons and the regulation of relevant cytochrome P-450 drug-metabolizing enzymes.